Medical Cell Biology Commons^™

M6a Associated Tsuc7 Inhibition Contributed To Erlotinib Resistance In Lung Adenocarcinoma Through A Notch Signaling Activation Dependent Way, Kai Li, Zi-Yang Peng, Shan Gao, Qing-Shi Wang, Rui Wang, Xiang Li, Guo-Dong Xiao, Jing Zhang, Hong Ren, Shou-Ching Tang, Xin Sun

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: The small tyrosine kinase inhibitors (TKIs) subversively altered the lung cancer treatments, but patients will inevitably face the therapy resistance and disease recurrence. We aim to explore the potential roles of non-coding RNAs in sensitizing the TKIs effects.

Methods: Multiple cellular and molecular detections were applied to confirm the mechanistic regulations and intracellular connections.

Results: We explored the specific gene features of candidates in association with resistance, and found that m6A controlled the stemness of EMT features through METTL3 and YTHDF2. The miR-146a/Notch signaling was sustained highly activated in a m6A dependent manner, and the m6A regulator of YTHDF2 …

Therapeutic Efficacy Of Mesenchymal Stem Cells For Cardiovascular Diseases, Dragana Radoje Miloradovic, Dragica Radoje Pavlovic, Miodrag Bozidar Stojkovic, Sanja Bratislav Bojic, Vladislav Bogdan Volarevic, Marina Milosav Gazdic Jankovic, Biljana Tomislav Ljujic

Journal of Mind and Medical Sciences

Despite the improvements in pharmacological and surgical treatments, cardiovascular diseases (CVDs) are the number one cause of death worldwide. During the last two decades, the search for new therapies has been revolutionized with the growing knowledge of stem cell biology. Due to their huge differentiation capacity and paracrine effects, mesenchymal stem cells (MSCs) are a promising tool for the treatment of CVDs. The encouraging outcomes of preclinical studies using MSCs as a treatment for diseased myocardium have set the scene for worldwide clinical trials. In this review, we overview either complete or ongoing clinical trials using MSCs for the therapy …

Cell-Based Therapies For Retinal Diseases: A Review Of Clinical Trials And Direct To Consumer "Cell Therapy" Clinics, John Hinkle, Raziyeh Mahmoudzadeh, Ajay E. Kuriyan

Wills Eye Hospital Papers

Background: The retinal pigment epithelium (RPE) is implicated in the pathophysiology of many retinal degenerative diseases. This cell layer is also an ideal target for cell-based therapies. Several early phase clinical trials evaluating cell therapy approaches for diseases involving the RPE, such as age-related macular degeneration and Stargardt's macular dystrophy have been published. However, there have also been numerous reports of complications from unproven "cell therapy" treatments marketed by "cell therapy" clinics. This review aims to outline the particular approaches in the different published clinical trials for cell-based therapies for retinal diseases. Additionally, the controversies surrounding experimental treatments offered outside …

Gβγ Regulates Mitotic Golgi Fragmentation And G2/M Cell Cycle Progression., Kalpana Rajanala, Lauren M. Klayman, Philip B. Wedegaertner

Department of Biochemistry and Molecular Biology Faculty Papers

Heterotrimeric G proteins (αβγ) function at the cytoplasmic surface of a cell's plasma membrane to transduce extracellular signals into cellular responses. However, numerous studies indicate that G proteins also play noncanonical roles at unique intracellular locations. Previous work has established that G protein βγ subunits (Gβγ) regulate a signaling pathway on the cytoplasmic surface of Golgi membranes that controls the exit of select protein cargo. Now, we demonstrate a novel role for Gβγ in regulating mitotic Golgi fragmentation, a key checkpoint of the cell cycle that occurs in the late G2 phase. We show that small interfering RNA-mediated depletion of …

Understanding The Effect Of Dietary Palmitic Acid On Glycolysis During Innate Immune Memory In Macrophages, Khaleda A. Aqaei

University Honors Theses

Trained immunity is long-term innate immune memory induced by a primary stimulus, which leads to hyper-inflammation upon secondary stimulation with a homologous or heterologous ligand. Trained immunity is mediated by epigenetic and metabolic reprogramming of the target cell and leads to modification of gene expression and cellular function. Classically, trained immunity is initiated by β-glucans, an inflammatory molecule found on the exterior of fungal species. Interestingly, our lab has recently described that dietary fatty acids can initiate trained immunity, working through similar pathways as β-glucans. Specifically, our data show that a pre-treatment with a specific dietary saturated fatty acid (SFA), …

Clinically Relevant Dosage Of Vancomycin Does Not Negatively Impact Periosteum Derived Osteoblast Precursor Cellular Functions, Alexis Hernandez

Seton Hall University Dissertations and Theses (ETDs)

Surgical site infections (SSI) can develop post-operatively and carry significant clinical and financial implications. SSI can carry a cost of up to $30,000 per case, as well as an estimated 6 day longer hospitalization. Patients with Type II Diabetes (DM) have an increased susceptibility to infection and suffer from poor bone healing overall. Therefore, diabetic patients who have undergone orthopedic surgery risk both an increased chance of developing an SSI as well as suboptimal bone healing. Vancomycin and other antibiotics have traditionally been used prophylactically to prevent infection, however the effect of vancomycin on bone healing in a diabetic population …

Placenta-Specific Slc38a2/Snat2 Knockdown Causes Fetal Growth Restriction In Mice, Owen R. Vaughan, Katarzyna Maksym, Elena Silva, Kenneth Barentsen, Russel V. Anthony, Sara L. Hillman, Thomas L. Brown, Rebecca Spencer, Anna L. David, Fredrick J. Rosario, Theresa L. Powell, Thomas Jansson

Neuroscience, Cell Biology & Physiology Faculty Publications

Fetal growth restriction (FGR) is a complication of pregnancy that reduces birth weight, markedly increases infant mortality and morbidity and is associated with later-life cardiometabolic disease. No specific treatment is available for FGR. Placentas of human FGR infants have low abundance of sodium-coupled neutral amino acid transporter 2 (Slc38a2/SNAT2), which supplies the fetus with amino acids required for growth. We determined the mechanistic role of placental Slc38a2/SNAT2 deficiency in the development of restricted fetal growth, hypothesizing that placenta-specific Slc38a2 knockdown causes FGR in mice. Using lentiviral transduction of blastocysts with a small hairpin RNA (shRNA), we achieved 59% knockdown of …

Comparative Analysis Of Proteomics Biomarkers Associated With Residual Ridge Resorption Induced By Denture Wear, Rohana Ahmad, Ainin Sofia Mohamad Napi, Tong Wah Lim, Su Keng Tan, Saiful Anuar Karsani, Musalmah Mazlan, Lay Kek Teh, Steven M. Morgano, Nadim Z. Baba

Makara Journal of Health Research

Background: The biochemical bone turnover markers for residual ridge resorption (RRR) are unclear. Therefore, the present study aimed to determine the biochemical bone turnover markers associated with RRR by comparing proteomics between the compressed mucosa of denture wearers and the non-compressed mucosa of non-denture wearers.

Methods: The mucosal specimens of 11 complete-denture wearers were obtained from the alveolar ridge during surgical implant exposure for implant-retained overdentures. All denture wearers had been edentulous and worn dentures for at least 5 years. The tissues of 11 non-denture wearers were taken from the ridge during minor preprosthetic surgery. The mucosal proteins …

Scrna Seq Analysis Of Ebv+ Associated Gastric Cancer, Eric Wang

Undergraduate Student Research Internships Conference

No abstract provided.

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

Vascular Disease Pathogenesis In Smooth Muscle Dysfunction Syndrome And Majewski Osteodysplastic Primordial Dwarfism Type Ii, Jamie Wright

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Vascular diseases are a leading cause of morbidity and mortality world-wide. Understanding their pathogenesis is crucial to better diagnosis and management of these life-threatening conditions. Through the study of rare mutations that lead to early onset and severe vascular diseases, we can elucidate underlying mechanisms for vascular disease pathogenesis and develop better treatments to prevent and manage more common causes of vascular diseases. In this study we look at two rare diseases that lead to severe vascular phenotypes, Smooth Muscle Dysfunction Syndrome (SMDS) and Majewski Osteodysplastic Primordial Dwarfism Type II (MOPDII). SMDS is a rare condition due to pathogenic variants …

Autophagy Regulation By Lipid Factors With Implications For Parkinson's Disease, Alejandro Soto-Avellaneda

Boise State University Theses and Dissertations

Parkinson’s disease is the second most common neurodegenerative disorder. It is characterized by the death of dopaminergic neurons in the substantia nigra and a series of debilitating motor symptoms. Macroautophagy (hereafter referred to as autophagy) is a cellular process by which cells degrade proteins, lipids, organelles or dysfunctional components. Autophagy is thought to play an important role in Parkinson’s disease, because it is the only cellular process known to remove large protein aggregates, such as those seen in Parkinson’s disease pathology. Historically, a large body of work has focused on reporting on protein effectors of autophagy, and regulation of autophagy …

Current State Of Preeclampsia Mouse Models: Approaches, Relevance, And Standardization, Christopher A. Waker, Melissa R. Kaufman, Thomas L. Brown

Neuroscience, Cell Biology & Physiology Faculty Publications

Preeclampsia (PE) is a multisystemic, pregnancy-specific disorder and a leading cause of maternal and fetal death. PE is also associated with an increased risk for chronic morbidities later in life for mother and offspring. Abnormal placentation or placental function has been well-established as central to the genesis of PE; yet much remains to be determined about the factors involved in the development of this condition. Despite decades of investigation and many clinical trials, the only definitive treatment is parturition. To better understand the condition and identify potential targets preclinically, many approaches to simulate PE in mice have been developed and …

The Role Of Action Potential Waveform In Failure Of Excitation Contraction Coupling, Xueyong Wang, Murad Nawaz, Steve R.A. Burke, Roger Bannister, Brent D. Foy, Andrew A. Voss, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Excitation contraction coupling (ECC) is the process by which electrical excitation of muscle is converted into force generation. Depolarization of skeletal muscle resting potential contributes to failure of ECC in diseases such as periodic paralysis, ICU acquired weakness and possibly fatigue of muscle during vigorous exercise. When extracellular K+ is raised to depolarize the resting potential, failure of ECC occurs suddenly, over a range of several mV of resting potential. While some studies have hypothesized the sudden failure of ECC is due to all-or-none failure of excitation, other studies suggest failure of excitation is graded. Intracellular recordings of action potentials …

A Rare Fatal Case Of Adenovirus Serotype 4 Associated Acute Disseminated Encephalomyelitis In An Adult: A Case Report, Zahra Qamar, Catherine Tucker, Lawrence C. Kenyon, Tricia. Royer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Acute disseminated encephalomyelitis (ADEM) is an autoimmune demyelinating disease directed against the myelin sheath of the central nervous system that typically presents 1–4 weeks after an infection or vaccination, most commonly in children. We describe a case of a young female who presented with rapidly progressive mental deterioration and died secondary to ADEM following an adenovirus upper respiratory tract infection.

Phenotypic Expansion Of Nucleolar Protein 6, A Potential Haplo-Essential Gene Contributing To Reproductive Failure, Alexandria N. Gonzalez

MEDI 8127 Scholarly Activities Pre-Clerkship

Haplo-essential genes are those which cannot tolerate a loss-of-function (LoF) mutation in a single allele. These essential genes are critical for cell survival (cell essential) and organism development (developmental essential). De novo LoF mutations of halpo-essential genes, therefore, likely contribute to reproductive failure in humans. Recently, Nucleolar protein 6 (Nol6), a protein coding gene, has been identified as an ideal candidate for phenotypic expansion for exploring genetic variants related to stillbirth [1]. Mouse embryos were edited via CRISPR/Cas9 reagents to induce a heterozygous LoF mutation in Nol6, followed by in vitro culture to blastocyst stage to experimentally …

Roles And Regulation Of Satellite Cells In Skeletal Muscle Regeneration, Sydney Vlasman

University Honors Theses

Skeletal muscle has an innate ability to self-regenerate in response to certain stimuli. In the case of trauma, muscle resident stem cells are required to meet the regenerative needs of the tissue. These resident stem cells, called satellite cells (SCs), are crucial in the regenerative process following injury; understanding the major factors which regulate satellite cell activity can provide valuable insight for regenerative medicine. The ability to implement and properly activate satellite cells has immense potential in the treatment of conditions including trauma, degenerative disorders, and age-related sarcopenia. This review will discuss the current understanding of satellite cell-mediated regeneration and …

Polθ Reverse Transcribes Rna And Promotes Rna-Templated Dna Repair, Gurushankar Chandramouly, Jiemin Zhao, Shane Mcdevitt, Timur Rusanov, Trung Hoang, Nikita Borisonnik, Taylor Treddinick, Felicia Wednesday Lopezcolorado, Tatiana Kent, Labiba Siddique, Joseph Mallon, Jacklyn Huhn, Zainab Shoda, Ekaterina Kashkina, Alessandra Brambati, Jeremy M Stark, Xiaojiang S Chen, Richard Pomerantz

Department of Biochemistry and Molecular Biology Faculty Papers

Genome-embedded ribonucleotides arrest replicative DNA polymerases (Pols) and cause DNA breaks. Whether mammalian DNA repair Pols efficiently use template ribonucleotides and promote RNA-templated DNA repair synthesis remains unknown. We find that human Polθ reverse transcribes RNA, similar to retroviral reverse transcriptases (RTs). Polθ exhibits a significantly higher velocity and fidelity of deoxyribonucleotide incorporation on RNA versus DNA. The 3.2-Å crystal structure of Polθ on a DNA/RNA primer-template with bound deoxyribonucleotide reveals that the enzyme undergoes a major structural transformation within the thumb subdomain to accommodate A-form DNA/RNA and forms multiple hydrogen bonds with template ribose 2'-hydroxyl groups like retroviral RTs. …

Immune Cells In Lens Injury Repair And Fibrosis, Janice L Walker, A. Sue Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Immune cells, both tissue resident immune cells and those immune cells recruited in response to wounding or degenerative conditions, are essential to both the maintenance and restoration of homeostasis in most tissues. These cells are typically provided to tissues by their closely associated vasculatures. However, the lens, like many of the tissues in the eye, are considered immune privileged sites because they have no associated vasculature. Such absence of immune cells was thought to protect the lens from inflammatory responses that would bring with them the danger of causing vision impairing opacities. However, it has now been shown, as occurs …

Synphilin-1 And Its Effects On Pathogenesis Of Parkinson’S Disease, Mirghani Mohamed

Honors Scholar Theses

Parkinson's Disease (PD) is a progressive neurodegenerative and movement disorder primarily caused by the degradation of dopaminergic neurons. Known markers of neurodegeneration in PD are Lewy Bodies, which are fibrillar aggregates that are found in the brains of PD patients. Lewy Bodies can accumulate from specific mutations in the SNCA gene that codes for alpha-synuclein, a protein enriched in presynaptic neurons. A mutated SNCA gene can cause conformational aggregates of alpha-synuclein to form toxic species mediating neuronal death. Research into alpha-synuclein has led to the discovery of a binding partner known as synphilin-1 that is also found in protein aggregates …